Objective To investigate the etiological and clinical characteristics of the outbreak of hand-foot-mouth disease (HFMD) in Chengdu in 2008. Methods A retrospective analysis was conducted to investigate 482 children with hand-foot-mouth disease in Chengdu from January to December 2008 in terms of epidemiology and clinical characteristics. Results Among the 482 children, 76.14% of the cases were infants, and male children numbered more than female ones. The proportion in the urban area was higher than that in the rural area. May to July was the peak epidemic period. Skin rash and fever were major clinical manifestations. Three cases were diagnosed as viral encephalitis. Conclusion The incidence of hand-foot-mouth disease is related to age and season. Effective prevention measures and isolated treatment are critical for prevention and therapy.